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[Confounding in nutritional epidemiology; is Mendelian randomization the answer?]
M B Katan1,2
1Vrije Universiteit Amsterdam, afd. Gezondheidswetenschappen, Amsterdam.
Nederlands Tijdschrift Voor Geneeskunde
|May 15, 2020
Summary
Observational studies often show health benefits from supplements and moderate alcohol, but clinical trials don't confirm them. Mendelian randomization suggests genetic factors, not just self-reporting, reveal true risks for alcohol and stroke.
Area of Science:
- Epidemiology
- Genetics
- Nutritional Science
Background:
- Observational studies frequently report positive health outcomes associated with vitamin and mineral supplements, as well as moderate alcohol consumption.
- However, randomized controlled trials (RCTs) have often failed to substantiate these observed benefits.
- This discrepancy may stem from unmeasured confounding factors and limitations in statistical adjustments within conventional epidemiological studies.
Purpose of the Study:
- To investigate the true association between alcohol intake and stroke risk, addressing potential confounding in observational data.
- To evaluate the utility of Mendelian randomization as a method to overcome limitations in conventional epidemiological research for dietary and lifestyle factors.
Main Methods:
- A Mendelian randomization study was conducted using data from approximately 500,000 Chinese individuals.
- Participants were analyzed based on both self-reported alcohol consumption and genetically predicted alcohol intake.
- Stroke risk was assessed across different levels of alcohol intake.
Main Results:
- Conventional analysis of self-reported alcohol intake showed a U-shaped curve for stroke risk, with the lowest risk at 1-2 units per day.
- Mendelian randomization analysis, which accounts for genetic predisposition to alcohol intake, revealed that stroke risk was lowest in abstainers and increased linearly with higher alcohol consumption.
- This suggests that the apparent benefits of moderate drinking observed in some studies may be due to confounding factors.
Conclusions:
- Mendelian randomization provides a more robust method for assessing the health effects of alcohol intake compared to traditional observational studies.
- The findings challenge the notion of a protective effect of moderate alcohol consumption on stroke risk.
- This approach may be superior for understanding the causal effects of diet and lifestyle on health outcomes.
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